Biochemistry chapter9 problem 15 (Berg, 8th)
Protease is the proteolytic enzymes that catabolise the peptides and proteins. HIV protease is an enzyme secreted by an HIV (retrovirus), it's a retroviral aspartyl protease function in the hydrolysis of the peptide bond during the life cycle of the virus. It helps in the enzymatic cleavage of the newly synthesized peptides (polyproteins) chain into a mature form of protein covering of the new virions.
Clinically, the protease inhibitors (PIs) are used as anti-viral drugs to prevent the viral infection and activation of new virion particles. These drugs interact with the active site of the protease site to prevent the viral replication and packaging of new infecting particles.
Aspartate is the protease enzyme main active site for its catalytic activity, PIs specifically binds to the active site of protease and loss enzymatic activity. Thereby, the after lytic phase viral particle are inactive.
There are two types of Mutation that result in drug resistance- "major" mutations (involves mutation on active site of protein-coding gene sequence) and "secondary" mutations (due to the prolonged effect of the drug, certain molecular changes occur on the periphery of the enzyme and reduce it effectivity). Mutation in HIV gene encodes for protease in the other amino acid coding region except for the active site amino acid sequence (aspartate) will not significantly affect the activity of protease activity and infection.
Biochemistry chapter9 problem 15 (Berg, 8th) 45 Viva la resistance. Many patients become resistant to HIV...
Many patients become resistant to HIV protease inhibitors with the passage of time owing to mutations in the HIV gene that encodes the protease. Provide a detailed rationale for the observation that mutations are not found in the active site aspartate residues.